Can improving phase 2 detoxification reduce the impact of food allergies?

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There has been an increase in the prevalence of food allergies over the past 20 years and it is now becoming an important public health issue.[1-3] Food allergies are defined as an adverse reaction arising from an immune response to a food or foods.[1] It can be described as a pathological reaction of the immune system triggered by the ingestion of a food protein antigen.[2] There is a complex multifactorial interplay of genetic variants, environmental exposures, gene-environment interactions, epigenetic alterations, and alterations in methylation and phase 1 and 2 detoxification.[3]

The most common food allergens include milk, egg, soy,[2] peanuts, tree nuts, fish, shellfish, wheat,[1,2] and gluten.[1] However, any food is capable of causing an allergy.[1] Symptoms can develop directly at the sites of allergen contact (e.g. mouth, oesophagus, intestine) or can be systemic in nature.[4] Some of the symptoms of food allergies include itching and swelling of the lips or tongue, abdominal discomfort, diarrhoea, nausea, itchy skin, anxiety and irritability.[1,4] Systemic reactions occur when allergens pass the barrier of the mucosa and enter into circulation.[4] It should be noted that food allergy is distinct from food intolerance in that an intolerance to a food or foods does not arise from immune system dysregulation.[2]

The term “detoxification” has become very common place, where it is generally referred to in weight loss programs or as a panacea for numerous nonspecific ailments.[5] So what is detoxification? Detoxification plays a major role in everyday life and is a continuous process. It is a large set of reactions that typically lower the toxicity and increase the water solubility of a wide range of endogenous and exdogenous compounds for excretion.[6]

There are numerous complex enzymatic mechanisms and pathways to detoxify these various compounds, such as the phase 1 (phase I) and phase 2 (phase II) detoxification enzyme systems.[7,8] Phase 1 detoxification involves the oxidation, peroxidation, hydroxylation and reduction of compounds, often by cytochrome P450 enzymes.[8] Whereas in phase 2 detoxification, the by-product of phase 1, or a pre-existing compound, is conjugated (combined or bound) to reduce toxicity and increase solubility.[6,8] This process leads to enhanced excretion in the bile and/or urine.[8]

For safe and efficient detoxification, a compound ideally undergoes a relatively slow phase 1 followed by a more rapid phase 2 detoxification for excretion. This process tends to prevent the accumulation of the phase 1 metabolites, which can become more toxic than the original compound.[9]

Several beneficial reactions occur during phase 2 detoxification, including amino acid conjugation, glucuronidation, glutathione conjugation (glutathionation), methylation and sulfation.[7] Factors influencing detoxification activity include diet, lifestyle, health status, genetic polymorphisms, age, gender, environment and disease.[7]

Nutrition plays a major role in the prevention and management of acute and chronic disease.[10] Although it might sound contradictory to use foods to manage food allergies, foods and food-based nutrients are known to modulate metabolic pathways involved in detoxification processes that may benefit people with food allergies.[8]

Phase 2 detoxification reactions require cofactors, either from foods or supplements.[7] Some of the foods that upregulate detoxification include cruciferous vegetables, broccoli, berries, citrus foods, garlic, onion, turmeric, astaxanthin and green tea.[8] Vitamin and mineral supplements,[5] N-acetylcysteine,[7] glutamine, glycine, taurine, bioflavonoids (quercetin),[8] probiotics.[5] resveratrol (e.g. from grapes and wine),[8] stool bulking agents and fibre, and various herbal medicines for the liver and gallbladder can also be utilised for improving the detoxification process.[5]

Utilising the phase 2 detoxification pathway to reduce the impact of food allergies is a novel approach. Further research is required to investigate the full effects of foods on detoxification and the effect of phase 2 detoxification on food allergies.


  1. Kulis M, et al. Diagnosis, management, and investigational therapies for food allergies. Gastroenterology 2015;148(6):1132-1142. [Abstract]
  2. Yu W, Freeland DMH, Nadeau K. Food allergy: immune mechanisms, diagnosis and immunotherapy. Nat Rev Immunol 2016;16(12):751-765. [Abstract]
  3. Hong X, Wang X. Early life precursors, epigenetics, and the development of food allergy. Semin Immunopathol 2012;34(5):655-669. [Abstract]
  4. Valenta R, et al. Food allergies: the basics. Gastroenterology 2015;148(6):1120-1131. [Abstract]
  5. Allen J, et al. Detoxification in naturopathic medicine: a survey. J Altern Complement Med 2011;17(12):1175-1180. [Full Text]
  6. Zimniak P. Detoxification reactions: relevance to aging. Ageing Res Rev 2008;7(4):281-300. [Abstract]
  7. Liska DJ. The detoxification enzyme systems. Altern Med Rev 1998;3(3):187-198. [Abstract]
  8. Hodges RE, Minich DM. Modulation of metabolic detoxification pathways using foods and food-derived components: A scientific review with clinical application. J Nutr Metab 2015;2015:760689. [Abstract]
  9. Houghton CA, Fassett RG, Coombes JS. Sulforaphane and other nutrigenomic Nrf2 activators: Can the clinician's expectation be matched by the reality? Oxid Med Cell Longev 2016;2016:7857186. [Abstract]
  10. McEwen BJ. The influence of diet and nutrients on platelet function. Semin Thromb Hemost2014;40(2):214-226. [Abstract]



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Dr Bradley McEwen

Dr Bradley McEwen PhD is a nutrition expert, naturopath, herbalist, educator, researcher, and mentor with over 19 years clinical experience. He received his Doctor of Philosophy (Medicine) from the University of Sydney and a Master of Health Science (Human Nutrition) from Deakin University, among other qualifications. He has numerous original research and review articles published in peer-reviewed journals. Bradley has a passion for education and research. His research interests include the effects of diet and nutrition on cardiovascular disease, diabetes, cardiometabolic syndrome, depression, anxiety, and polycystic ovary syndrome. Bradley has a strong passion for seeing people succeed and achieve their goals.